Rapid and Robust Identification of Sepsis Using SeptiCyte RAPID in a Heterogeneous Patient Population

Robert Balk; Annette M Esper; Greg S Martin; Russell R Miller 3rd; Bert K Lopansri; John P Burke; Mitchell Levy; Richard E Rothman; Franco R D'Alessio; Venkataramana K Sidhaye; Neil R Aggarwal; Jared A Greenberg; Mark Yoder; Gourang Patel; Emily Gilbert; Jorge P Parada; Majid Afshar; Jordan A Kempker; Tom van der Poll; Marcus J Schultz; Brendon P Scicluna; Peter M C Klein Klouwenberg; Janice Liebler; Emily Blodget; Santhi Kumar; Xue W Mei; Krupa Navalkar; Thomas D Yager; Dayle Sampson; James T Kirk; Silvia Cermelli; Roy F Davis; Richard B Brandon

doi:10.3390/jcm13206044

Rapid and Robust Identification of Sepsis Using SeptiCyte RAPID in a Heterogeneous Patient Population

J Clin Med. 2024 Oct 10;13(20):6044. doi: 10.3390/jcm13206044.

Authors

Robert Balk¹, Annette M Esper², Greg S Martin², Russell R Miller 3rd³, Bert K Lopansri^{4

5}, John P Burke^{4

5}, Mitchell Levy⁶, Richard E Rothman⁷, Franco R D'Alessio⁸, Venkataramana K Sidhaye⁷, Neil R Aggarwal⁹, Jared A Greenberg¹, Mark Yoder¹, Gourang Patel¹, Emily Gilbert¹⁰, Jorge P Parada¹⁰, Majid Afshar¹¹, Jordan A Kempker², Tom van der Poll¹², Marcus J Schultz^{13

14}, Brendon P Scicluna^{15

16}, Peter M C Klein Klouwenberg¹⁷, Janice Liebler^{18

19}, Emily Blodget^{18

19}, Santhi Kumar^{18

19}, Xue W Mei²⁰, Krupa Navalkar²¹, Thomas D Yager²¹, Dayle Sampson²¹, James T Kirk²¹, Silvia Cermelli²¹, Roy F Davis²¹, Richard B Brandon²¹

Affiliations

¹ Rush Medical College and Rush University Medical Center, Chicago, IL 60612, USA.
² Grady Memorial Hospital and Emory University School of Medicine, Atlanta, GA 30322, USA.
³ FirstHealth of the Carolinas, Pinehurst, NC 28374, USA.
⁴ Intermountain Medical Center, Murray, UT 84107, USA.
⁵ School of Medicine, University of Utah, Salt Lake City, UT 84132, USA.
⁶ Warren Alpert Medical School, Brown University, Providence, RI 02912, USA.
⁷ School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
⁸ Pulmonary and Critical Care & Sleep Medicine, Department of Medicine, University of Miami, Miami, FL 33136, USA.
⁹ Anschutz Medical Campus, University of Colorado, Denver, CO 80045, USA.
¹⁰ Loyola University Medical Center, Maywood, IL 60153, USA.
¹¹ School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA.
¹² Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
¹³ Division of Cardiothoracic and Vascular Anesthesia and Intensive Care Medicine, Department of Anesthesia, General Intensive Care, and Pain Management, Medical University of Vienna, 1090 Vienna, Austria.
¹⁴ Nuffield Department of Medicine, University of Oxford, Oxford OX1 2JD, UK.
¹⁵ Centre for Molecular Medicine and Biobanking, University of Malta, Msida MSD 2080, Malta.
¹⁶ Department of Applied Biomedical Science, Faculty of Health Sciences, Mater Dei Hospital, University of Malta, Msida MSD 2080, Malta.
¹⁷ Fundashon Mariadal, Kralendijk, Bonaire, Netherlands Antilles.
¹⁸ Keck Hospital of University of Southern California (USC), Los Angeles, CA 90033, USA.
¹⁹ Los Angeles General Medical Center, Los Angeles, CA 90033, USA.
²⁰ Princeton Pharmatech, Princeton, NJ 08540, USA.
²¹ Immunexpress Inc., Seattle, WA 98109, USA.

Abstract

Background/Objective: SeptiCyte RAPID is a transcriptional host response assay that discriminates between sepsis and non-infectious systemic inflammation (SIRS) with a one-hour turnaround time. The overall performance of this test in a cohort of 419 patients has recently been described [Balk et al., J Clin Med 2024, 13, 1194]. In this study, we present the results from a detailed stratification analysis in which SeptiCyte RAPID performance was evaluated in the same cohort across patient groups and subgroups encompassing different demographics, comorbidities and disease, sources and types of pathogens, interventional treatments, and clinically defined phenotypes. The aims were to identify variables that might affect the ability of SeptiCyte RAPID to discriminate between sepsis and SIRS and to determine if any patient subgroups appeared to present a diagnostic challenge for the test. Methods: (1) Subgroup analysis, with subgroups defined by individual demographic or clinical variables, using conventional statistical comparison tests. (2) Principal component analysis and k-means clustering analysis to investigate phenotypic subgroups defined by unique combinations of demographic and clinical variables. Results: No significant differences in SeptiCyte RAPID performance were observed between most groups and subgroups. One notable exception involved an enhanced SeptiCyte RAPID performance for a phenotypic subgroup defined by a combination of clinical variables suggesting a septic shock response. Conclusions: We conclude that for this patient cohort, SeptiCyte RAPID performance was largely unaffected by key variables associated with heterogeneity in patients suspected of sepsis.

Keywords: SIRS; SeptiCyte; host immune response; phenotype; sepsis; sepsis likelihood; stratification.

Grants and funding

This work was funded by Immunexpress, Inc.